A transcription factor response element for gene expression during circadian night
A transcription factor response element for gene expression during circadian night
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DOI：
10.1038/nature00906
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发表时间：
2002-08-01
期刊：
影响因子：
64.8
通讯作者：
Hashimoto, S
中科院分区：
文献类型：
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作者：
Ueda, HR;Chen, WB;Hashimoto, S
哺乳动物的生物钟由复杂的集成反馈环路(1-10)组成，如果没有系统动力学的全面测量和网络结构的确定(11)，就无法阐明这些环路。为了剖析这样一个复杂的系统，我们采取了基于基因组、分子和细胞生物学技术的系统生物学方法。我们描述了在光/暗周期和恒定黑暗下视交叉上核和肝脏全基因组的表达模式。我们为新发现的循环基因确定了人类同源基因的转录起始点，然后进行了生物信息学搜索，以寻找特定时间表达与转录起始点周围的转录因子反应元件之间的关系。在这里，我们展示了REV-ERBA/ROR反应元件在昼夜基因表达中的作用，该反应元件与BMal1同相，与PER2振荡相反。这一作用通过体外验证系统得到验证，在体外验证系统中，瞬时转染时钟控制报告载体的培养成纤维细胞显示出强大的昼夜生物发光(12)。
Mammalian circadian clocks consist of complex integrated feedback loops(1-10) that cannot be elucidated without comprehensive measurement of system dynamics and determination of network structures(11). To dissect such a complicated system, we took a systems-biological approach based on genomic, molecular and cell biological techniques. We profiled suprachiasmatic nuclei and liver genome-wide expression patterns under light/dark cycles and constant darkness. We determined transcription start sites of human orthologues for newly identified cycling genes and then performed bioinformatical searches for relationships between time-of-day specific expression and transcription factor response elements around transcription start sites. Here we demonstrate the role of the Rev-ErbA/ROR response element in gene expression during circadian night, which is in phase with Bmal1 and in antiphase to Per2 oscillations. This role was verified using an in vitro validation system, in which cultured fibroblasts transiently transfected with clock-controlled reporter vectors exhibited robust circadian bioluminescence(12).